Conventional cancer therapeutic approaches, including radiation and chemotherapy, are nonselective and damage normal cells. Gene therapies have exhibited limited success. This likely is because the vector or virus inefficiently reaches the targeted tumor and/or the agents used in gene therapy interact with normal cells and to yield adverse effects (McCormick, Nat. Rev. Cancer, 1: 130-141 (2001), and Scanlon, Anticancer Res., 24: 501-504 (2004)).
TGFβ targeted therapies, such as neutralizing antibodies, small molecular inhibitors, and adenoviruses have been used in preclinical and clinical settings (Dumont et al., Cancer Cell, 3: 531-536 (2003)). However, TGFβ is well known to work as a tumor suppressor in early stage tumorigenesis and as a tumor promoter in later stages of tumor progression (Yang et al., Cancer Res., 68: 9107-9111 (2008), and Yang et al, Trends Immunol., 31: 220-227 (2010). The underlying mechanisms for this switch in function are not clear and pose a great challenge for TGFβ targeted therapies. This challenge in TGFβ targeted therapy represents a general problem of cancer biology, as many cancer related molecules demonstrate a dual role of pro- and anti-cancer properties.
Thus, there remains a need for effective and specific treatment of cancer for both animals and humans.